One year after: What are the implications of the new ESC/EAS LDL-c - - PowerPoint PPT Presentation

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One year after: What are the implications of the new ESC/EAS LDL-c - - PowerPoint PPT Presentation

Aug 14, 2023 466 likes •711 views

EBAC Accredited symposium during Digital ESC 2020 PCSK9i & LDL-c: Guidelines, Practice & Innovation: Review of facts and opportunities ESC virtual congress, August, 2020 One year after: What are the implications of the new ESC/EAS LDL-c

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  • Prof. François Mach, MD, FESC

Cardiology Department Geneva University Hospital Switzerland Francois.Mach@hcuge.ch

EBAC Accredited symposium during Digital ESC 2020 PCSK9i & LDL-c: Guidelines, Practice & Innovation: Review of facts and opportunities ESC virtual congress, August, 2020

One year after: What are the implications of the new ESC/EAS LDL-c Guidelines for PCSK9i?

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No financial conflicts of interest

All my honoraria for conferences and advisory board are intended for the GEcor Foundation, which supports cardiovascular research within Geneva University Hospital.

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Characteristics of lipoproteins

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Time-exposure to low LDL-c

Eur Heart J 2017;38:2459

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Source of evidence Mean reduction in LDL cholesterol; mmol/L [mg/dL] Outcome RR (95% CI) CTT meta-analysis1 (high-intensity vs standard statin; subgroup <2.0 mmol/L) 1.71 [66] vs 1.32 [50] MI, CHD death, stroke, coronary revasc. 0.71 (0.56-0.91) [per mmol/L] IMPROVE-IT2 (eze plus statin vs statin) 1.80 [70] vs 1.40 [54] CV death, MI, stroke, UA, coronary revasc 0.94 (0.89-0.99) FOURIER3 (evolocumab plus high-dose statin ± eze vs high-dose statin ± eze) 2.37 [92] vs 0.78 [30] CV death, MI, stroke, UA, coronary revasc 0.85 (0.79-0.92) ODYSSEYOUTCOMES4 (alirocumab plus high- dose statin ± eze vs high-dose statin ± eze) 2.37 [92] vs 1.37 [53] MI, CHD death, stroke, UA 0.85 (0.78-0.93)

Evidence for efficacy of LDL-lowering therapies

1.Lancet 2010; 376: 1670-81; 2. NEJM 2015; 372: 2387-97; 3. NEJM 2017; 376: 1713-22; 4. NEJM 2018; 379: 2097-107

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PCSK9 mAb: Efficacy and safety

Lancet 2017;390:1962

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Can J Cardiol 2018;34:1600

PCSK9 mAb: Efficacy and safety

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Eur Heart J 2020;41:111-188

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Concepts for lipid lowering treatment

▪ Define CV risk (very high-risk patients) ▪ Define LDL-C goals and targets ▪ Choose best lipid-lowering strategies

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Cardiovascular risk categories (2)

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Recommendations for low-density lipoprotein cholesterol lowering (1)

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Recommendations for low-density lipoprotein cholesterol lowering (2)

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Recommendations for low-density lipoprotein cholesterol lowering (2)

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Recommendations for pharmacological low-density lipoprotein cholesterol lowering (3)

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Recommendations for lipid-lowering therapy in very-high-risk patients with acute coronary syndromes (1)

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Recommendations for lipid-lowering therapy in very-high-risk patients with acute coronary syndromes (2)

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Intensity of pharmacological LDL lowering

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2016 vs 2019 ESC/EAS Lipid Guidelines

Category Recommendation

Very high risk

  • CVD
  • DM with target organ

damage

  • Severe CKD (GFR <30

mL/min/1.73 m2 LDL-C goal of <1.8 mmol/L (70 mg/dL). If baseline LDL-C is 1.8 – 3.5 mmol/L (70 and 135 mg/dL) a reduction of ≥50% should also be achieved. High Risk

  • Markedly elevated singe

risk factors, in particular cholesterol >8 mmol/L (>310 mg/dL) (e.g. FH) or BP ≥180/110 mmHg.

  • Most other people with

DM

  • Moderate CKD (GFR 30-59

mL/min/1.73 m2

  • A calculated SCORE ≥5%

and <10% for 10-year risk

  • f fatal CVD.

LDL-C goal of <2.6 mmol/L (100 mg/dL). At least a 50% reduction from baseline, if >2.6 mmol/L (100 mg/dL) should also be achieved.

Category Recommendation

Very high risk

  • Documented ASCVD
  • DM with target organ damage. ≥3 major

risk factors or early onset of T1DM of >20 years.

  • SCORE ≥10% for 10-year risk of fatal CV.
  • FH with ASCVD or with another major

risk factor.

  • Severe CKD (GFR <30 mL/min/1.73 m2

LDL-C reduction of ≥50% from baseline and an LDL-C goal of <1.4 mmol/L (55 md/dL) High Risk

  • Markedly elevated singe risk factors, in

particular total cholesterol >8 mmol/L (>310 mg/dL), LDL-C >4.9 mmol/L (>190 mg/dL),or BP ≥180/110 mmHg.

  • Patients with FH without other major

risk factors.

  • DM without target organ damage, with

DM duration >10 years or other additional risk factors.

  • Moderate CKD (GFR 30-59 mL/min/1.73

m2

  • SCORE ≥5% and <10% for 10-year risk of

fatal CVD. LDL-C reduction of ≥50% from baseline and an LDL-C goal of <1.8 mmol/L (70 md/dL)

  • 1. Eur Heart J 2016;37:2999-3058
  • 2. Eur Heart J 2020;41:111-188

2019 ESC/EAS2 2016 ESC/EAS1

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Opportunities and challenges for the future

Efficacy of different approaches to lipid lowering

Nature Rev Cardiol 2018;15:261

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Concept change II: Treat (much more) aggressively

From desirable target to “LDL-C elimination in the blood”

The modern concept of lipid-lowering strategies to reduce cardiovascular diseases

Concept change I: Start Early

Less “lipid-exposure” leads to prevention of lesion formation

Concept change III: Use combination therapy

Statin + Ezetimibe (+/- PCSK9mAb) induced LDL-C lowering reduces CV-risk